Viruses and autoimmune liver disease

Autoimmune hepatitis is characterized by hypergammaglobulinemia, female predominance, autoantibodies and a good response to immunosuppression, and is based on specific autoantibodies and clinical characteristics. Several subgroups may be distinguished. As in most autoimmune diseases, the etiology is unknown. The association of autoimmune hepatitis with a viral etiology is most prominent in autoimmune hepatitis type 2 which is characterized by liver/kidney microsomal (LKM-1) autoantibodies against cytochrome P-450 II D6. Depending on the geographical origin of the patients, a specific proportion of patients with autoimmune hepatitis type 2 is associated with hepatitis C virus infection. These HCV RNA-positive patients are older, female predominance is not profound, and response to immunosuppression is generally low compared to the HCV-negative patients with autoimmune hepatitis type 2. The genetic background is unclear. HCV sequence analysis revealed that HCV genotype II is prominent in HCV-positive autoimmune hepatitis type 2. HCV mutants with deletions in the HCV envelope region were identified. The relevance of these HCV mutants for the induction of autoimmunity needs to be characterized further. The HCV-negative population of patients with autoimmune hepatitis type 2 seems to have a relation with herpes simplex virus (HSV-1) infection since the B-cell epitope of cytochrome P-450 II D6, the major LKM-1 antigen, shares sequence homology with the IE-175 protein of HSV-1. In the HCV-negative population of autoimmune hepatitis type 2, HLA-DR3 and C4-AQ0 alleles are significantly increased.